Long-term proton pump inhibitors use and its association with premalignant gastric lesions: a systematic review and meta-analysis
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ABSTRACT:
SUBMITTER: Zheng Z
PROVIDER: S-EPMC10492503 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related gastrointestinal diseases. Recently, some studies have reported that PPIs can alter the gastric mucosal architecture; however, the relationship remains controversial. This meta-analysis study was designed to quantify the association between long-term PPI administration and gastric atrophy.A PubMed search was conducted to identify studies using the keywords proton pump inhibitors or PPI and gastric atrophy or atrophic gastritis; the timeframe of publication searched was up to May 2016. Heterogeneity among studies was tested with the Q test; odds ratios (OR) and 95% confidence intervals (CI) were calculated. P values were calculated by I2 tests and regarded as statistically significant when <0.05.We identified 13 studies that included 1465 patients under long-term PPI therapy and 1603 controls, with a total gastric atrophy rate of 14.50%. There was a higher presence of gastric atrophy (15.84%; statistically significant) in PPI group compared to the control group (13.29%) (OR: 1.55, 95% CI: 1.00-2.41).The pooled data suggest that long-term PPI use is associated with increased rates of gastric atrophy. Large-scale multicenter studies should be conducted to further investigate the relationship between acid suppressants and precancerous diseases.
| S-EPMC5539675 | biostudies-other
Project description:BackgroundProton-pump inhibitors (PPIs) are among the most prescribed medicines worldwide and concern about their long-term use is growing. We used dispensing claims for every person in Australia dispensed publicly subsidized PPIs between 2013 and 2016 to determine the incidence and prevalence of PPI use and to examine the patterns and durations of PPI treatment among individuals continuing treatment beyond the guideline-recommended maximum 12 weeks.MethodsWe estimated annual prevalence and incidence per 100 people and duration of treatment for every Australian dispensed publicly subsidized PPIs between 2013 and 2016. We examined patterns of PPI treatment in three patient subgroups using PPIs for more than 12 weeks duration; people receiving maintenance, long-term continuous or long-term intermittent treatment. We calculated the proportion in each subgroup stepping down from higher to lower PPI strengths, stepping up from lower to higher PPI strength and discontinuing treatment.ResultsPPIs were dispensed to 4,388,586 people; 60% were women; median age at initiation was 52 years [interquartile range (IQR): 36-65]. Standard and high strength PPIs accounted for 95% of dispensings. Annual incidence and prevalence were 3.9/100 and 12.5/100, respectively, in 2016 and highest among individuals over 65 years (prevalence range: 33-43/100). Most people (67%) stopped treatment after one dispensing; while 25%, 6% and 10% continued on maintenance, long-term continuous and long-term intermittent treatment, respectively. Median duration of treatment in people continuing treatment was 501 days (IQR: 180-not reached) for maintenance treated individuals and 'not reached' for long-term treated individuals. We observed 35%, 20% and 47% of people stepping down from higher to lower treatment strengths on maintenance, long-term continuous and long-term intermittent treatment, respectively.ConclusionsLonger-term treatment with higher strength PPIs is common. Targeted regulation of PPI prescribing may improve the uptake of lower strength formulations and reduce both harms and costs associated with long-term PPI treatment.
| S-EPMC7082869 | biostudies-literature
Project description:Background: This study aimed to systematically analyze the association between long-term use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). Methods: We performed a systematic search of articles on the relationship between long-term use of PPIs and the risk of GC from PubMed and EMBASE. We calculated the pooled odds ratio of GC in PPI users compared to non-PPI users using random-effects models. Results: This meta-analysis included 18 studies from 20 different databases with 4348,905 patients enrolled. In the random effects model, we found that an increased risk of GC among PPI users (OR = 1.94; 95% CI [1.43, 2.64]). The long-term use of PPIs compared with histamine-2 receptor antagonist users did not increase the risk of GC (OR = 1.65; 95% CI [0.92, 2.97]). Stratified analysis showed that PPI users had a significantly increased risk of noncardia GC (OR = 2.53; 95% CI [2.03, 3.15]), but had a relatively small relationship with the risk of gastric cardia cancer. (OR = 1.79; 95% CI [1.06, 3.03]). With the extension of PPI use time, the estimated risk value decreases (<1 year: OR = 6.33, 95% CI [3.76, 10.65]; 1–3 years: OR = 1.82, 95% CI [1.30, 2.55]; >3 years: OR = 1.25, 95% CI [1.00, 1.56]). Despite Helicobacter pylori eradication, the long-term use of PPIs did not alter the increased risk of GC (OR = 2.29; 95% CI [1.57, 3.33]). Conclusion: Our meta-analysis found that PPI use may be associated with an increased risk of GC. Further research on the causal relationship between these factors is necessary.
| S-EPMC9750528 | biostudies-literature
Project description:IntroductionProton pump inhibitors (PPIs) are one of the most prescribed classes of drugs worldwide as a first-line treatment of acid-related disorders. Although adverse effects are rare and rapidly reversible after a short exposure, concerns have been recently raised about a greater toxicity on cardiovascular health after a longer exposure, especially when combined with clopidogrel. We aimed to evaluate the safety of long-term PPI use on cardiovascular health in patients with known atheromatous cardiovascular disease.MethodsA literature search was conducted in the PubMed, Embase, and Cochrane Library databases and grey literature in April 2022. Articles published between 2014 and 2022 were considered relevant if they were designed as randomized controlled trials (RCTs) that included post hoc analyses or prospective observational studies and if they investigated clinical cardiovascular outcomes associated with PPI use for 6 months or more in patients suffering from cardiovascular disease requiring antiplatelet agent therapy and/or coronary angioplasty. Statistical analyses were performed using RevMan 5.4 software (Computer program, the Cochrane Collaboration, 2020, London, UK). The risk of bias was assessed using the Cochrane risk-of-bias tool for the RCTs and the Newcastle-Ottawa scale for the observational studies.ResultsA total of 10 full-text articles involving 53,302 patients were included. Substantial heterogeneity was found among the 10 included studies. The primary analysis showed no significant differences between the PPI group and the control group for the risks of major adverse cardiovascular events (MACEs), all-cause death (ACD), or target vessel revascularization (TVR) using a random-effects model (OR 1.15, 95% CI 0.98-1.35, p = 0.08, I2 = 73%; OR 1.24, 95% CI 0.94-1.65, p = 0.13, I2 = 63%; and OR 1.19, 95% CI 0.76-1.87, p = 0.45, I2 = 61%, respectively). The primary analysis yielded similar results for the risks of myocardial infarction (MI), stroke, and cardiovascular death (CVD) using a fixed-effects model (OR 0.98, 95% CI 0.88-1.09, p = 0.66, I2 = 0%; OR 1.02, 95% CI 0.90-1.17, p = 0.73, I2 = 0%; and OR 1.04, 95% CI 0.94-1.16, p = 0.44, I2 = 35%, respectively). Likewise, a subgroup analysis based on eight randomized controlled trials failed to identify any association between PPI use and the risks of MACEs, MI, stroke, TVR, ACD, or CVD using a fixed-effects model (overall pooled OR 1.01, 95% CI 0.96-1.06; p = 0.66; I2 = 0%). The pulled data from the two included observational studies (OS) demonstrated a significantly increased risk of MACEs in the PPI group (OR 1.42, 95% CI [1.29-1.57], p <0.001; I2 = 0%). In another subgroup analysis, no evidence of an increased risk of adverse cardiovascular events in the co-therapy PPI/clopidogrel versus clopidogrel alone groups was found with the exception of the risk of ACD (OR 1.50, 95% CI 1.23-1.82, p = 0.001, I2 = 0%). Nevertheless, after performing a sensitivity analysis reaching heterogeneity I2 = 0%, the co-prescription of PPIs and clopidogrel was at increased risk of MACEs (p < 0.001), CVD (p = 0.008), and TVR (p < 0.001) but remained statistically non-significant for the risk of MI (p = 0.11).ConclusionsThe overall results of this meta-analysis showed that long-term PPI use was not associated with an increased risk of adverse cardiovascular events. However, inconsistent results were found for combined PPI/clopidogrel therapy. These results should be considered with caution in light of the significant heterogeneity, the limited number of included studies, and the lack of adjustment for potential confounders.
| S-EPMC9322047 | biostudies-literature
Project description:BackgroundProton pump inhibitors [PPIs] are widely used to treat a number of gastro-oesophageal disorders. PPI-induced elevation in intragastric pH may alter gastrointestinal physiology. The tight junctions [TJs] residing at the apical intercellular contacts act as a paracellular barrier. TJ barrier dysfunction is an important pathogenic factor in inflammatory bowel disease [IBD]. Recent studies suggest that PPIs may promote disease flares in IBD patients. The role of PPIs in intestinal permeability is not clear.AimThe aim of the present study was to study the effect of PPIs on the intestinal TJ barrier function.MethodsHuman intestinal epithelial cell culture and organoid models and mouse IBD models of dextran sodium sulphate [DSS] and spontaneous enterocolitis in IL-10-/- mice were used to study the role of PPIs in intestinal permeability.ResultsPPIs increased TJ barrier permeability via an increase in a principal TJ regulator, myosin light chain kinase [MLCK] activity and expression, in a p38 MAPK-dependent manner. The PPI-induced increase in extracellular pH caused MLCK activation via p38 MAPK. Long-term PPI administration in mice exaggerated the increase in intestinal TJ permeability and disease severity in two independent models of DSS colitis and IL-10-/- enterocolitis. The TJ barrier disruption by PPIs was prevented in MLCK-/- mice. Human database studies revealed increased hospitalizations associated with PPI use in IBD patients.ConclusionsOur results suggest that long-term use of PPIs increases intestinal TJ permeability and exaggerates experimental colitis via an increase in MLCK expression and activity.
| S-EPMC10115233 | biostudies-literature
Project description:Background & aimsBacterial infections, particularly repeated infections, are significant causes of morbidity and mortality among patients with cirrhosis. We investigated and characterized risk factors for repeat infections in these patients.MethodsIn a prospective study, we collected data from 188 patients hospitalized with cirrhosis and infections and enrolled in the North American Consortium for the Study of End-Stage Liver Disease (12 centers). Patients were followed up for 6 months after hospital discharge and data were analyzed on type of infections and factors associated with subsequent infections.ResultsSix months after hospital discharge, 14% of subjects had received liver transplants, 27% died, and 59% were alive without liver transplantation. After discharge, 45% had subsequent infections, but only 26% of the subsequent infections occurred at the same site. Compared with patients not re-infected, patients with repeat infections were older and a higher proportion used proton pump inhibitors (PPIs) (P = .006), rifaximin (P < .001), or prophylactic therapy for spontaneous bacterial peritonitis (SBP) (P < .001). Logistic regression showed that SBP prophylaxis (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.56-7.63), PPI use (OR, 2.94; 95% CI, 1.39-6.20), SBP at hospital admission (OR, 0.37; 95% CI, 0.15-0.91), and age (OR, 1.06; 95% CI, 1.02-1.11) were independent predictors of subsequent infections.ConclusionsPatients hospitalized with cirrhosis and infections are at high risk for subsequent infections, mostly at different sites, within 6 months of index infection resolution. Those at highest risk include previously infected older patients receiving PPIs and/or SBP prophylaxis, although these associations do not prove that these factors cause the infections. New strategies are needed to prevent infections in patients with cirrhosis.
| S-EPMC4326601 | biostudies-literature
Project description:Evidence from preclinical studies suggests a preventive effect of proton pump inhibitors (PPIs) in preeclampsia. Recently, several epidemiological studies have described a conflicting association between the use of PPIs during pregnancy and preeclampsia risk. This study aimed to evaluate the association between PPI use and the risk of preeclampsia. We searched databases, including MEDLINE, Embase, Scopus, Web of Science Core Collection, Emcare, CINAHL, and the relevant grey literature from inception until 13 September 2021. Studies reporting the preeclampsia risk with the use of PPIs were eligible for inclusion. Literature screening, data extraction, and the risk of bias assessment were performed independently by two investigators. Random-effect meta-analysis was performed to generate relative risks (RR) and 95% confidence intervals (CI). The risk of preeclampsia and preterm preeclampsia among women receiving PPIs during pregnancy were the primary outcomes of interest. This meta-analysis comprised three studies involving 4,877,565 pregnant women, of whom 119,017 were PPI users. The included studies were judged to have a low risk of bias. The risk of preeclampsia among pregnant women who received PPIs anytime during pregnancy was significantly increased (RR 1.27 (95% CI: 1.23-1.31)), although the increase was trivial in absolute terms (2 per 1000). The subgroup analysis revealed that the risk was increased in each of the three trimesters. The risk of preterm preeclampsia among pregnant women receiving PPIs anytime during pregnancy was not significantly increased (RR 1.04 (95% CI: 0.70-1.55)). The certainty evaluated by GRADE in these estimates was low. PPI use may be associated with a trivial increase in the risk of preeclampsia in pregnant women. There is no evidence supporting that PPI use decreases the risk of preeclampsia or preterm preeclampsia.
| S-EPMC9410414 | biostudies-literature
Project description:A 52-year-old man who had been using a proton pump inhibitor (PPI) and a potassium-competitive acid blocker (P-CAB) for 14 years underwent esophagogastroduodenoscopy and was found to have three neuroendocrine tumors (NETs) in the gastric body. Following detailed examinations, parietal cell dysfunction was excluded, and the NETs did not meet the criteria for the Rindi classification types I-III. The lesions were ultimately considered to be associated with the long-term use of the PPI and P-CAB. We performed endoscopic submucosal dissection of the lesions, with no recurrence or new lesions noted after discontinuation of the PPI and P-CAB.
| S-EPMC11309866 | biostudies-literature
Project description:ObjectivesTo estimate associations between long-term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care.DesignLongitudinal analyses of electronic medical records.SettingEngland PARTICIPANTS: Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age- and sex-matched controls (N=75,050).MeasurementsNet hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures.ResultsDuring the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR-adjusted hazard ratio=1.82, 95% confidence interval=1.27-2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score- and inverse probability-weighted models.ConclusionIn a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short-term harms of PPIs should not divert attention from potential long-term effects of PPI prescriptions on older adults.
| S-EPMC6099478 | biostudies-literature
Project description:BackgroundProton pump inhibitors (PPIs) are a first-line treatment for EoE, but data are limited concerning response durability. We aimed to determine long-term outcomes in EoE patients responsive to PPI-therapy.MethodsWe conducted a retrospective cohort study of newly diagnosed adults with EoE who had initial histologic response (<15 eosinophils per high-power-field) to PPI-only therapy. We extracted data regarding their subsequent clinical course and outcomes. We compared findings between the initial PPI-response endoscopy and the final endoscopy, and assessed factors associated with loss of PPI response.ResultsOf 138 EoE patients with initial histologic response to PPI, 50 had long-term endoscopic follow-up, 40 had clinical follow-up, 10 changed treatments, and 38 had no long-term follow-up. Of those with endoscopic follow-up, mean follow-up-time was 3.6 ± 2.9 years; 30 and 32 patients (60%; 64%) maintained histologic and symptom responses, respectively. However, fibrotic endoscopic findings of EoE were unchanged. Younger age (aOR 1.05, 95% CI: 1.01-1.11) and dilation prior to PPI treatment (aOR 0.21, 95% CI: 0.05-0.83) were the only factors associated with long-term loss of PPI response.ConclusionsLong-term histologic and clinical response rates for PPI therapy were 60% and 64%, respectively. Younger age and dilation at baseline were associated with histologic loss of response. These data can inform long-term EoE treatment selection.
| S-EPMC9427674 | biostudies-literature